Birch reaction products are asymmetrically hydrogenated with high enantio- and diastereoselectivity via iridium catalysts. This new method of producing chiral compounds was explored for a variety of 1,3-di- and 1,2,4-tri-substituted cyclohexadienes.

Tetrahydroisoquinoline (TIQ) derivatives exhibit good biological activity. However, utilization of TIQ compounds in asymmetric catalysis is limited. This paper presents a series of TIQ derivatives in asymmetric transfer hydrogenation (ATH) reactions. Chiral TIQ amino alcohol ligands were synthesized and screened for the ATH reaction of aromatic ketones. The effect of a cis- and trans-phenyl substitution at the C-1 position on the ligand backbone was investigated both experimentally and computationally. The results showed that the trans orientation on the TIQ scaffold yields higher turnover rates with a selectivity of 94% ee obtained at room temperature with an Ru complex. The cis isomer results in a high turnover rate with no selectivity. The trans isomer gave 99% ee at lower temperatures. Furthermore, it was observed that substitution at the C-3-alpha position results in a drop of the enantioselectivity and the reactivity of the catalyst.

A novel family of tetrahydroisoquinoline (TIQ) phosphine-oxazoline ligands and four corresponding iridium complexes have been developed and applied to the asymmetric hydrogenation of unfunctionalized olefins. The results showed that the best conversion rates were observed in up to 99% with an enantiomeric excess of 91%.

Diphenylvinylphosphine oxides and di- and trisubstituted vinylphosphonates have been employed as substrates in iridium-catalyzed asymmetric hydrogenations. Complete conversions and excellent enantioselectivities (up to and above 99% ee) were observed for a range of substrates with both aromatic and aliphatic groups at the prochiral carbon. We have also hydrogenated electron-deficient carboxyethylvinylphosphonates with excellent stereoselectivity (up to and above 99% ee). The hydrogenated products of both classes of substrates are synthetically useful intermediates.

Fluorine-containing compounds are useful in many applications ranging from pharmaceuticals to ferroelectric crystals. We have developed a new, highly enantioselective synthetic route to trifluoromethyl-bearing stereocenters in up to 96% ee via asymmetric hydrogenation using N,P-ligated iridium catalysts. We also hydrogenated an isomeric mixture of olefins; this reaction gave the hydrogenation product highly enantioselectively (87% ee), and only the E isomer was present after the reaction had reached 56% conversion.

A series of new phosphine-thiazole compounds has been synthesized and used as efficient ligands in the palladium-catalyzed asymmetric intermolecular Heck coupling of 2,3-dihydrofuran with aryl triflates and cyclohexenyl triflate. Microwave heating was used to accelerate the reactions and gave complete conversions in as little as one hour. Products were obtained with good to excellent enantioselectivities.

A novel family of eleven new tetrahydroisoquinoline (TIQ)-oxazoline intermediates and five corresponding copper(II) catalysts has been developed and applied to the catalytic asymmetric Henry reaction of various aldehydes with nitromethane to provide beta-hydroxy nitroalkanes in high conversion (>99%) This paper describes the synthesis of the TIQ compounds from L-dihydroxyphenylalanine (L-DOPA) as the starting material The chiral ligands were complexed in situ with various transition metals such as Cu, Sc, Co, Zn, Ni and Mn and tested as a chiral catalyst for the Henry reaction The reaction was optimized in terms of the metal, counter ion, solvent, temperature and over a range of substrates The corresponding catalyst with copper(II) acetate and 2-propanol as the solvent provides the best enantioselectivities (up to 77% ee) of the corresponding nitroalcohol for 4-chlorobenzaldehyde.

New bicyclic thiazole-based chiral N,P-chelating ligands were developed. High activities and enantioselectivities were achieved in the iridium-catalyzed asymmetric hydrogenation of olefins with the new ligands.

A library of readily available phosphite-oxazole/thiazole ligands (L1 a-g-L7 a-g) was applied in the Ir-catalyzed asymmetric hydrogenation of several largely unfunctionalized E- and Z-trisubstituted and 1,1-disubstituted terminal alkenes. The ability of the catalysts to transfer chiral information to the product could be tuned by choosing suitable ligand components (bridge length, the substituents in the heterocyclic ring and the alkyl backbone chain, the configuration of the ligand backbone, and the substituents/configurations in the biaryl phosphite moiety), so that enantioselectivities could be maximized for each substrate as required. Enantioselectivities were therefore excellent (enantiomeric excess (ee) values up to >99 %) for a wide range of E- and Z-trisubstituted and 1,1-disubstituted terminal alkenes. The biaryl phosphite moiety was a very advantageous ligand component in terms of substrate versatility.

A new class of modular P,N-ligand library has been synthesized and screened in the Pd-catalyzed allylic substitution reactions of several substrate types. These series of ligands can be prepared efficiently from easily accessible hydroxyl-oxazole/thiazole derivatives. Their modular nature enables the bridge length, the substituents at the heterocyclic ring and in the alkyl backbone chain, the configuration of the ligand backbone, and the substituents/configurations in the biaryl phosphite moiety to be easily and systematically varied. By carefully selecting the ligand components, therefore, high regio- and enantioselectivities (ee values up to 96 %) and good activities are achieved in a broad range of mono-, di-, and trisubstituted linear hindered and unhindered substrates and cyclic substrates. The NMR spectroscopic and DFT studies on the Pd-pi-allyl intermediates provide a deeper understanding of the effect of ligand parameters on the origin of enantioselectivity.

New chiral diamine ligands have been synthesized and evaluated in the asymmetric Ru-catalyzed hydrogenation of prochiral aryl ketones. All catalysts showed good conversions with observed enantioselectivities ranging from moderate to good.

The use of the tetrahydroisoquinoline scaffold is well documented in biologically active compounds. However, reports of the utilisation of tetrahydroisoquinoline compounds in asymmetric catalysis are limited. The synthesis of novel diamine ligands possessing the tetrahydroisoquinoline (tetrahydroisoquinoline) backbone and evaluation of their activity in the asymmetric transfer hydrogenation of acetophenone are presented. The diamine ligands in conjunction with i-PrOH as the hydrogen source and [RhCl2(Cp*)](2) as the metal precursor proved to be the most effective of the tetrahydroisoquinoline derivatives for this catalytic system. Water was found to have a profound influence on the enantioselectivity of the reaction. Optimisation of the amount water, i-PrOH and catalytic loading content rendered the best result of 70% enantioselectivity for the (S)-1-phenylethanol isomer product.

Diarylimethine-containing stereocenters are present in pharmaceuticals and natural products, making the synthetic methods that form these chiral centers are important in industry. We have applied iridium complexes with novel N,P-chelating ligands to the asymmetric hydrogenation of trisubstituted olefins, forming diarylmethine chiral centers in high conversions and excellent enantioselectivities (up to 99% ee) for a broad range of substrates. Our results support the hypothesis that steric hindrance in one specific area of the catalyst is playing a key role in stereoselection, as the hydrogenation of substrates differing little at the prochiral carbon occurred with high enantioselectivity. As a result, excellent stereodiscrimination was obtained even when the prochiral carbon bore, for example, phenyl and p-tolyl groups.

A range of saturated chiral azacycles has been prepared in high yield and with high selectivity from simple starting materials. A modular approach with ring-closing metathesis as a key step was used to produce a number of five-, six-, and seven-membered cyclic alkenes. Asymmetric hydrogenation catalyzed by N,P-ligated iridium complexes gave saturated azacycles in high optical purity. This methodology was demonstrated in the synthesis of a pharmaceutical precursor.

New diastereomeric N,P-ligands, derived from the natural product (+)--pinene, have been synthesized and evaluated in iridium-catalyzed asymmetric hydrogenation. The ligands are tetrahydroquinoline derivatives synthesized directly from commercially available -pinene utilizing resolution or recrystallization to separate diastereomers. In reduction of a range of different trisubstituted alkenes the catalysts express very different activities ranging from no activity to high activity. One of the catalysts gives good ee values for some substrates.